Do P2Y12 receptor inhibitors prescribed poststroke modify the risk of cognitive disorder or dementia? Protocol for a target trial using multiple national Swedish registries
Introduction The target of a class of antiplatelet medicines, P2Y12R inhibitors, exists both on platelets and on brain immune cells (microglia). This protocol aims to describe a causal (based on a counterfactual model) approach for analysing whether P2Y12R inhibitors prescribed for secondary prevent...
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BMJ Publishing Group
2022-05-01
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| Series: | BMJ Open |
| Online Access: | https://bmjopen.bmj.com/content/12/5/e058244.full |
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| author | John Attia Michael Nilsson Frederick R Walker Christopher Oldmeadow Michael Pollack Jenny Nyberg Sara Gustavsson N David Åberg Georg Hans Kuhn Madeleine Hinwood Marina Ilicic Chris Levi Sarah J Johnson Leeanne M Carey Lucy Leigh Neil Spratt Thomas Lindén |
| author_facet | John Attia Michael Nilsson Frederick R Walker Christopher Oldmeadow Michael Pollack Jenny Nyberg Sara Gustavsson N David Åberg Georg Hans Kuhn Madeleine Hinwood Marina Ilicic Chris Levi Sarah J Johnson Leeanne M Carey Lucy Leigh Neil Spratt Thomas Lindén |
| author_sort | John Attia |
| collection | DOAJ |
| description | Introduction The target of a class of antiplatelet medicines, P2Y12R inhibitors, exists both on platelets and on brain immune cells (microglia). This protocol aims to describe a causal (based on a counterfactual model) approach for analysing whether P2Y12R inhibitors prescribed for secondary prevention poststroke may increase the risk of cognitive disorder or dementia via their actions on microglia, using real-world evidence.Methods and analysis This will be a cohort study nested within the Swedish National Health and Medical Registers, including all people with incident stroke from 2006 to 2016. We developed directed acyclic graphs to operationalise the causal research question considering potential time-independent and time-dependent confounding, using input from several experts. We developed a study protocol following the components of the target trial approach described by Hernan et al and describe the data structure that would be required in order to make a causal inference. We also describe the statistical approach required to derive the causal estimand associated with this important clinical question; that is, a time-to-event analysis for the development of cognitive disorder or dementia at 1, 2 and 5-year follow-up, based on approaches for competing events to account for the risk of all-cause mortality. Causal effect estimates and the precision in these estimates will be quantified.Ethics and dissemination This study has been approved by the Ethics Committee of the University of Gothenburg and Confidentiality Clearance at Statistics Sweden with Dnr 937-18, and an approved addendum with Dnr 2019-0157. The analysis and interpretation of the results will be heavily reliant on the structure, quality and potential for bias of the databases used. When we implement the protocol, we will consider and document any biases specific to the dataset and conduct appropriate sensitivity analyses. Findings will be disseminated to local stakeholders via conferences, and published in appropriate scientific journals. |
| format | Article |
| id | doaj-art-a2c72b5d00fc4bf3916f0f580c4206ed |
| institution | OA Journals |
| issn | 2044-6055 |
| language | English |
| publishDate | 2022-05-01 |
| publisher | BMJ Publishing Group |
| record_format | Article |
| series | BMJ Open |
| spelling | doaj-art-a2c72b5d00fc4bf3916f0f580c4206ed2025-08-20T02:17:00ZengBMJ Publishing GroupBMJ Open2044-60552022-05-0112510.1136/bmjopen-2021-058244Do P2Y12 receptor inhibitors prescribed poststroke modify the risk of cognitive disorder or dementia? Protocol for a target trial using multiple national Swedish registriesJohn Attia0Michael Nilsson1Frederick R Walker2Christopher Oldmeadow3Michael Pollack4Jenny Nyberg5Sara Gustavsson6N David Åberg7Georg Hans Kuhn8Madeleine Hinwood9Marina Ilicic10Chris Levi11Sarah J Johnson12Leeanne M Carey13Lucy Leigh14Neil Spratt15Thomas Lindén16Department of Medicine, John Hunter Hospital, University of Newcastle Hunter Medical Research Institute, Newcastle, New South Wales, Australia4 University of Newcastle Hunter Medical Research Institute, New Lambton, New South Wales, Australia2 Hunter Medical Research Institute, New Lambton Heights, New South Wales, AustraliaHunter Medical Research Institute, Newcastle, New South Wales, AustraliaUS Evidence, AstraZeneca Pharmaceuticals LP, Wilmington, Delaware, USA5 Section for Clinical Neuroscience, Institute of Neuroscience and Physiology, University of Gothenburg, Gothenburg, Sweden3 Department of Forensic Genetics and Forensic Toxicology, National Board of Forensic Medicine, Linköping, Sweden8 Department of Acute Medicine and Geriatrics, Sahlgrenska University Hospital, Goteborg, Region Västra Götaland, Sweden1 Center for Brain Repair and Rehabilitation, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden1 School of Medicine and Public Health, The University of Newcastle, Callaghan, New South Wales, AustraliaHunter Medical Research Institute, New Lambton Heights, New South Wales, Australia2 Hunter Medical Research Institute, New Lambton Heights, New South Wales, Australia4 Department of Cellular Pathology, Royal Victoria Hospital, Newcastle upon Tyne, UK1 Occupational Therapy, School of Allied Health, Human Services and Sport, La Trobe University, Melbourne, Victoria, AustraliaHunter Medical Research Institute, New Lambton Heights, New South Wales, Australia2 Hunter Medical Research Institute, New Lambton Heights, New South Wales, Australiaconsultant in neurology and psychiatryIntroduction The target of a class of antiplatelet medicines, P2Y12R inhibitors, exists both on platelets and on brain immune cells (microglia). This protocol aims to describe a causal (based on a counterfactual model) approach for analysing whether P2Y12R inhibitors prescribed for secondary prevention poststroke may increase the risk of cognitive disorder or dementia via their actions on microglia, using real-world evidence.Methods and analysis This will be a cohort study nested within the Swedish National Health and Medical Registers, including all people with incident stroke from 2006 to 2016. We developed directed acyclic graphs to operationalise the causal research question considering potential time-independent and time-dependent confounding, using input from several experts. We developed a study protocol following the components of the target trial approach described by Hernan et al and describe the data structure that would be required in order to make a causal inference. We also describe the statistical approach required to derive the causal estimand associated with this important clinical question; that is, a time-to-event analysis for the development of cognitive disorder or dementia at 1, 2 and 5-year follow-up, based on approaches for competing events to account for the risk of all-cause mortality. Causal effect estimates and the precision in these estimates will be quantified.Ethics and dissemination This study has been approved by the Ethics Committee of the University of Gothenburg and Confidentiality Clearance at Statistics Sweden with Dnr 937-18, and an approved addendum with Dnr 2019-0157. The analysis and interpretation of the results will be heavily reliant on the structure, quality and potential for bias of the databases used. When we implement the protocol, we will consider and document any biases specific to the dataset and conduct appropriate sensitivity analyses. Findings will be disseminated to local stakeholders via conferences, and published in appropriate scientific journals.https://bmjopen.bmj.com/content/12/5/e058244.full |
| spellingShingle | John Attia Michael Nilsson Frederick R Walker Christopher Oldmeadow Michael Pollack Jenny Nyberg Sara Gustavsson N David Åberg Georg Hans Kuhn Madeleine Hinwood Marina Ilicic Chris Levi Sarah J Johnson Leeanne M Carey Lucy Leigh Neil Spratt Thomas Lindén Do P2Y12 receptor inhibitors prescribed poststroke modify the risk of cognitive disorder or dementia? Protocol for a target trial using multiple national Swedish registries BMJ Open |
| title | Do P2Y12 receptor inhibitors prescribed poststroke modify the risk of cognitive disorder or dementia? Protocol for a target trial using multiple national Swedish registries |
| title_full | Do P2Y12 receptor inhibitors prescribed poststroke modify the risk of cognitive disorder or dementia? Protocol for a target trial using multiple national Swedish registries |
| title_fullStr | Do P2Y12 receptor inhibitors prescribed poststroke modify the risk of cognitive disorder or dementia? Protocol for a target trial using multiple national Swedish registries |
| title_full_unstemmed | Do P2Y12 receptor inhibitors prescribed poststroke modify the risk of cognitive disorder or dementia? Protocol for a target trial using multiple national Swedish registries |
| title_short | Do P2Y12 receptor inhibitors prescribed poststroke modify the risk of cognitive disorder or dementia? Protocol for a target trial using multiple national Swedish registries |
| title_sort | do p2y12 receptor inhibitors prescribed poststroke modify the risk of cognitive disorder or dementia protocol for a target trial using multiple national swedish registries |
| url | https://bmjopen.bmj.com/content/12/5/e058244.full |
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